Deleted Gene Found That is Common to Autism and Kidney Issues

September 28, 2016
Deleted Gene Found That is Common to Autism and Kidney Issues
Source: Kim Gunkel/Getty Images

Newly published data from a team of investigators from the Developmental Biology Institute of Marseille and the University of Manchester have identified a link between kidney issues and autism spectrum disorder (ASD) in children that could have a signficant impact on how physicians treating both conditions administer tests to their patients.

The new study describes the effects of mutations within a gene scientists colloquially named Teashirt in humans and mice. The gene, formally named TSHZ3, has been previously implicated by the joint research team in 2008 as being essential for the development of smooth muscle in the wall of the ureter. Mutant mice were born with "blown-up" kidneys because their ureters failed to propel urine actively down to the bladder.

Scientists subsequently identified a patient born with abnormal kidneys that had a deleted TSHZ3 gene while also displaying characteristics of ASD. When the research team went back and looked at mice with the TSHZ3 mutation, they discovered that not only did the mice have kidney problems, but they also displayed learning difficulties.

"The mutant mouse kidney looks just like hydronephrosis, the distended kidney seen in about 1 in 1000 individuals when they are screened by sonar scans as unborn babies," explained co-author Adrian Woolf, M.D., chair of pediatric science at the University of Manchester. “It now appears that this gene is linked to at least some of these cases and that it also has implications for how our brains work in childhood."

The findings from this study were published recently in Nature Genetics in an article entitled “TSHZ3 Deletion Causes an Autism Syndrome and Defects in Cortical Projection Neurons.”

The findings ignited a global search of other kidney clinics, which returned 10 more patients with similar symptoms. After genetic testing, it was confirmed that the same gene was missing in all of them—findings that are published in the new paper.

The authors wrote that they identified "TSHZ3 as the critical region for a syndrome associated with heterozygous deletions at 19q12-q13.11, which includes autism spectrum disorder (ASD). In Tshz3-null mice, differentially expressed genes include layer-specific markers of cerebral cortical projection neurons (CPNs), and the human orthologs of these genes are strongly associated with ASD.”

The researchers are hopeful with this new data in hand that physicians will begin to test for mutations and deletions of the TSHZ3 gene, allowing for treatment therapies to start as early as possible.

"Early detection of this new condition will favor early behavioral therapies, which is good for the kids and their family," remarked senior study author Laurent Fasano, Ph.D., group leader at the Developmental Biology Institute of Marseille and discoverer of the Teashirt gene in 1991.

The research team was excited by their findings and believe that the link between the two diseases has implications for how doctors work with patients who display either kidney or learning problems.

"A fairly simple genetic test on patients being treated for either kidney problems or ASD could identify whether the Teashirt gene is missing and also highlight that the patient may need investigation for the other condition,” concluded Dr. Woolf. “Time will tell whether TSHZ3 plays a role in many more cases than we've currently been able to identify."